Exploring the role of the radioprotector amifostine in locally advanced non-small cell lung cancer: Radiation therapy oncology group trial 98-01

Abstract

The ultimate goal of any strategy in oncology is to enhance the therapeutic ratio, defined as tumor cell kill divided by normal tissue injury. Whereas most trials focus on intensifying therapy, this often increases toxicity so that there is no overall gain in the therapeutic ratio. Radiation Therapy Oncology Group (RTOG) trial 98-01, a phase III study testing the ability of a radioprotector (Amifostine [Ethyol, WR-2721]) to reduce the toxicity of an intensive chemoradiation regimen for locally advanced non-small cell lung cancer (NSCLC), is unique in that it addresses both "sides" of this equation. During the 1990s, thoracic radiotherapy (RT) combined with chemotherapy was accepted as a "new" gold standard for patients with good performance status locally advanced/inoperable NSCLC. This paradigm shift away from RT alone has raised several key questions: What is the optimal method of integrating chemotherapy and RT? Equally importantly, how can the toxicity of combined modality strategies be reduced? This article will review the background underlying RTOG 98-01, a trial exploring the potential role of amifostine in NSCLC.